Qin Xianyan, He Liming, Fan Donghao, Liang Wenlang, Wang Qin, Fang Jiyu
Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Advanced Materials Processing and Analysis Center and Department of Materials Science and Engineering, University of Central Florida, Florida 32816, United State.
Asian J Pharm Sci. 2021 Jul;16(4):483-493. doi: 10.1016/j.ajps.2021.03.001. Epub 2021 Mar 23.
Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint inflammation and immune dysfunction. Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications, the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems. Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation. Ac2-26, a 25-amino acid peptide derived from Annexin A (a pro-resolving mediator), has shown good efficacy in the treatment of inflammatory disorders. However, the low bioavailability of Ac2-26 peptides hinders their efficacy . In this paper, we formed PEGylated lipid nanoparticles (LDNPs) by the co-assembly of l-ascorbyl palmitate (L-AP) and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE-PEG) to encapsulate and deliver Ac2-26 peptides to the arthritic rats. They showed good stability and biocompatibility. After being intravenously administrated, Ac2-26 peptide-loaded PEGylated lipid nanoparticles (ADNPs) showed the prolonged circulation time and enhanced accumulation in inflamed sites. therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology. Therefore, the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.
类风湿性关节炎（RA）是一种常见的自身免疫性疾病，其特征为关节炎症和免疫功能障碍。尽管在临床应用中已采用多种治疗方法来治疗RA，但RA患者的低反应性和不良的全身毒性仍是尚未解决的问题。用促消退介质靶向炎症的消退途径将激发患者对抗炎症的保护作用。Ac2-26是一种源自膜联蛋白A（一种促消退介质）的25个氨基酸的肽，在治疗炎症性疾病方面已显示出良好的疗效。然而，Ac2-26肽的低生物利用度阻碍了它们的疗效。在本文中，我们通过将棕榈酸l-抗坏血酸酯（L-AP）和N-（羰基甲氧基聚乙二醇-2000）-1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺（DSPE-PEG）共组装形成聚乙二醇化脂质纳米颗粒（LDNPs），以将Ac2-26肽包封并递送至关节炎大鼠体内。它们表现出良好的稳定性和生物相容性。静脉注射后，负载Ac2-26肽的聚乙二醇化脂质纳米颗粒（ADNPs）显示出延长的循环时间和在炎症部位的积累增加。治疗评估显示，ADNPs可减轻滑膜炎症并改善关节病理状况。因此，使用ADNPs的促消退治疗策略在RA治疗中是有效的。
